The overall objective of this grant has been to resolve major questions about the biochemistry of normal connective tissues and about human diseases that alter these tissues. The first project will begin true protein engineering of collagen by defining the structure and function of a series of recombinant collagens. fibromodulin and decorin; and critical determinants for fibril assembly that can help define details for the assembly process. The second project will use the strategy of DNA linkage analysis and positional cloning or "reverse genetics" to define the gene or genes at fault causing spinal deformities such as spondylolysis and osteoperosis.